BI21 The development of diffuse extragenital lichen sclerosus in a patient on palbociclib and fulvestrant for metastatic breast cancer
Authors: Sarah Johnston, Maneesha Vatve, Lianne Thomas
Journal: British Journal of Dermatology (2023)

Abstract A 59-year-old woman with skin phototype VI was commenced on palbociclib (cyclin-dependent kinase 4/6 inhibitor) and fulvestrant (oestrogen receptor antagonist) as chemotherapy agents for metastatic breast cancer. Two months later, she developed a new widespread rash. Past medical history included atopic dermatitis but no autoimmune conditions. Denosumab was her only other medication. On examination, she had hyperpigmented thickened plaques with purple hue and sclerotic plaques with cigarette wrinkling on her buttocks, arms, neck, abdomen and axillae. She also had widespread hypopigmentation. Biopsies showed hyperkeratosis and a lichenoid inflammatory reaction with pigmentary incontinence. Clinicopathological correlation supported the diagnosis of extragenital lichen sclerosus (EGLS). Palbociclib and fulvestrant were stopped and she noted improvement of her rash within 3 weeks. She was also managed with potent topical steroids, which eased her symptoms and further improved the appearance. Lichen sclerosus (LS) is a chronic inflammatory condition affecting the anogenital area. EGLS occurs in approximately 15–20% of those with LS, and only 6% of patients with EGLS do not have genital involvement at diagnosis. LS and EGLS are characterized by white papules, sclerosus and erosions with atrophic plaques. In the skin of colour, the presentation is varied, with hypo- or hyperpigmentation. Currently, the pathogenesis of EGLS is poorly understood, with studies suggesting an autoimmune aetiology, with possible genetic, infectious, hormonal, trauma and drug associations. In addition to specific autoantibodies, the absence of a suppressive function of regulatory T cells may contribute to the induction of autoimmunity. A recent association with immune checkpoint inhibitors (ICIs) further establishes this link. There are 12 case reports of ICIs and LS/EGLS, but cell cycle inhibitors associated with EGLS have not yet been reported (Silvestri M, Cristaudo A, Morrone A et al. Emerging skin toxicities in patients with breast cancer treated with new cyclin-dependent kinase 4/6 inhibitors: a systematic review. Drug Saf 2021; 44:725–32). Laboratory studies demonstrate increased T-cell activation with abemaciclib, a cell cycle inhibitor, which has been hypothesized to have other autoimmune drug associations (Truong K, Jones-Caballero M, Chou S et al. Lichen sclerosus and immune checkpoint inhibitors: a case and review of the literature. Australas J Dermatol 2023; 64:158–61). Other possible theories contributing to the development of EGLS include the Koebner effect of deep intramuscular injection of fulvestrant or subsequent low-oestrogen state. To the best of our knowledge, this is the first case of EGLS following these chemotherapy agents. This case hypothesizes the role of cell cycle inhibitors contributing to the aetiology in a mechanism similar to that of ICIs. It also demonstrates the difference in presentation of EGLS in skin of colour.